DESCRIPTION: For patients with metastatic renal cell carcinoma (RCC), treatment with IL-2 or IL-2 + Interferon-alpha is a well-established therapeutic option. However, the clinical results fail to achieve the success seen in pre-clinical models. One possible explanation is that patients with progressively growing tumors develop immune dysfunction making it difficult to achieve a therapeutic response to immune therapy unless the treatment first corrects this alteration. Traditional cellular assays have demonstrated alterations in T-cell and antigen-presenting cell function in cancer; however, the basis for these changes has been poorly understood. Recent reports have identified alterations which include an arrest in dendritic cell maturation and a decreased expression of some T-cell signal transduction proteins that could in part explain this cellular immune dysfunction. Preliminary results suggest that some of these changes correlate with the stage of the disease and the survival of patients. Additional data also suggests that the dendritic and T-cell alterations are corrected in patients responding to treatment, but persist in those who do not respond. Therefore, our hypothesis is that the induction of therapeutic anti-tumor immune response requires the presence of a competent immune system prior to treatment or the use of therapies that correct the defects in the immune response. The preliminary data needs to be evaluated in a well-controlled randomized immunotherapy trial. We now have a unique opportunity to further evaluate these immune alterations in a Phase III randomized multi-institutional trial comparing the therapeutic efficacy of IL-2 with IL-2 + Interferon-alpha in RCC patients. Therefore the present protocol aims to: 1) Determine how frequently patients with advanced renal cell carcinoma present an arrest in the maturation of dendritic cells or alteration in T-cell signal transduction molecules; 2) To compare these alterations with clinical prognostic factors, and the levels of soluble factors such as IL-6, IL-10, VEGF, and Fas-ligand; 3) To determine the changes in immune function present in patients with dendritic cells or T-cell alterations; 4) To determine whether a successful immunotherapy leads to the correction of T-cell signal transduction alterations or the re-expression of normal costimulatory molecules on dendritic cells.